The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells

Moon,Ji-Hong; Hong,Jeong-Min; Park,Sang-Youel

doi:10.3892/mmr.2021.12069

The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells

Authors:
- Ji-Hong Moon
- Jeong-Min Hong
- Sang-Youel Park
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Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea
Published online on: April 7, 2021 https://doi.org/10.3892/mmr.2021.12069
Article Number: 430
Copyright: © Moon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prion diseases, which involve the alteration of cellular prion protein into a misfolded isoform, disrupt the central nervous systems of humans and animals alike. Prior research has suggested that peroxisome proliferator‑activator receptor (PPAR)γ and autophagy provide some protection against neurodegeneration. PPARs are critical to lipid metabolism regulation and autophagy is one of the main cellular mechanisms by which cell function and homeostasis is maintained. The present study examined the effect of troglitazone, a PPARγ agonist, on autophagy flux in a prion peptide (PrP) (106‑126)‑mediated neurodegeneration model. Western blot analysis confirmed that treatment with troglitazone increased LC3‑II and p62 protein expression, whereas an excessive increase in autophagosomes was verified by transmission electron microscopy. Troglitazone weakened PrP (106‑126)‑mediated neurotoxicity via PPARγ activation and autophagy flux inhibition. A PPARγ antagonist blocked PPARγ activation as well as the neuroprotective effects induced by troglitazone treatment, indicating that PPARγ deactivation impaired troglitazone‑mediated protective effects. In conclusion, the present study demonstrated that troglitazone protected primary neuronal cells against PrP (106‑126)‑induced neuronal cell death by inhibiting autophagic flux and activating PPARγ signals. These results suggested that troglitazone may be a useful therapeutic agent for the treatment of neurodegenerative disorders and prion diseases.

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